NE 52-QQ57 | CAS#1401728-56-0 | GPR4 antagonist

MedKoo Cat#: 555805 | Name: NE 52-QQ57

Description:

WARNING: This product is for research use only, not for human or veterinary use.

NE52-QQ57 is an orally available GPR4 antagonist with an IC50 of 70 nM. NE 52-QQ57 significantly inhibited the AGE-induced increased expression of several key inflammatory cytokines and signaling molecules, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase 2 (COX2), and prostaglandin E2 (PGE2).

Chemical Structure

NE 52-QQ57

CAS#1401728-56-0

Theoretical Analysis

MedKoo Cat#: 555805

Name: NE 52-QQ57

CAS#: 1401728-56-0

Chemical Formula: C24H28N6O

Exact Mass: 416.2325

Molecular Weight: 416.53

Elemental Analysis: C, 69.21; H, 6.78; N, 20.18; O, 3.84

Price and Availability

Size	Price	Availability
5mg	USD 150.00	Ready to ship
10mg	USD 250.00	Ready to ship
25mg	USD 450.00	Ready to ship
50mg	USD 750.00	Ready to ship
100mg	USD 1,250.00	Ready to ship
200mg	USD 1,950.00	Ready to ship
500mg	USD 2,850.00	Ready to ship
1g	USD 3,650.00	Ready to ship
2g	USD 6,450.00	Ready to ship

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Related CAS #

No Data

Synonym

NE52-QQ57; NE-52-QQ57; NE 52-QQ57; NE52QQ57; NE-52QQ57; NE 52QQ57;

IUPAC/Chemical Name

2-(4-((2-ethyl-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)phenyl)-5-(piperidin-4-yl)-1,3,4-oxadiazole

InChi Key

HXPQWNPLNIEJOW-UHFFFAOYSA-N

InChi Code

InChI=1S/C24H28N6O/c1-4-21-20(22-26-15(2)13-16(3)30(22)29-21)14-17-5-7-18(8-6-17)23-27-28-24(31-23)19-9-11-25-12-10-19/h5-8,13,19,25H,4,9-12,14H2,1-3H3

SMILES Code

CCC1=NN(C(C)=CC(C)=N2)C2=C1CC3=CC=C(C4=NN=C(C5CCNCC5)O4)C=C3

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Osteoarthritis (OA) is a common degenerative joint disease for which an effective therapeutic strategy has not yet been established. AGEs are widely recognized as a contributor to OA pathogenesis. GPR4, a recently discovered proton-sensing transmembrane receptor, has been shown to possess a wide range of physiological functions. However, the potential role of this receptor in chondrocytes and the pathogenesis of OA is unclear.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A21T03K01

View CoA: current batch, Lot#T20D08P12

QC Data

View QC data: current batch, Lot#T20D08P12

View QC data: current batch, Lot#A21T03K01

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

NE 52-QQ57 is a selective, and orally available GPR4 antagonist with an IC50 of 70 nM. NE 52-QQ57 has anti-inflammatory activity.

In vitro activity:

The effect of NE 52-QQ57 on proton-mediated cAMP accumulation in cells over-expressing GPR4 was dependent on pH (Fig. 3A) and this dependence in the acidic range could be explained by competition with protons. NE 52-QQ57 (100nM) was maximally effective at pH 7.7 but approximately equally effective at pH 8.0 and 7.4. At pH 7.1, the potency of NE 52-QQ57 was reduced and at pH 6.8 NE 52-QQ57 (100nM) was ineffective. At pH 7.4, NE 52-QQ57 acts as a highly potent antagonist of GPR4 mediated cAMP accumulation with IC50 of 26.8nM (Fig. 3B). Reference: Neuropharmacology. 2018 Aug;138:381-392. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29894771/

In vivo activity:

Minute ventilation (VE) which is the cumulative of RR and VT was not significantly affected at baseline by 20 mg kg−1 of NE-52-QQ57 in either rats (n = 8) or mice (n = 10). Relative to the vehicle (25% DMSO), NE-52-QQ57 significantly attenuated VE during hypercapnia at 5 and 10% CO2 in both species. For example, with 10% CO2 VE increased to 216 ± 11 a.u. in the group treated with vehicle, but only to 164 ± 18 a.u. in mice treated with NE-52-QQ57 (p < 0.001). Similarly, in rats at 10% CO2 VE increased to 662 ± 40 a.u. in the vehicle group, but to 568 ± 22 a.u. in the treated group (p < 0.001). Thus, in freely behaving mice and rats NE22-QQ57 blunted hypercapnic response to CO2. In anaesthetised rats, hypercapnia (10% CO2 in the inspired air) increased respiratory rate from 77 ± 9 to 94 ± 13 bursts/min (Fig. 6A), and this was not affected following systemic administration of NE 52-QQ57 (20 mg kg−1; n = 8, 76 ± 9 to 95 ± 12 bursts min−1; p = 0.92). NE 52-QQ57 had no effect on CO2-evoked increases in diaphragm EMG amplitude (0.25 ± 0.03 to 0.33 ± 0.04V cf. 0.25 ± 0.02 to 0.34 ± 0.03V; p = 0.94) and minute ventilation (19 ± 3 to 32±7A.U cf. 20 ± 3 to 33±6A.U; p = 0.88). Systemic NE 52-QQ57 also had no effect on basal respiratory rate (Fig. 6B). To additionally ensure that NE 52-QQ57 reaches the central GPR4 targets, the drug was then delivered directly on the ventral surface of the brainstem, where the RTN is located. Hypercapnia (10% CO2 in the inspired air) in 7 animals with denervated peripheral chemoreceptors increased respiratory frequency, phrenic nerve amplitude and minute ventilation (Fig. 6C). Hypercapnia increased the respiratory rate from 18 ± 6 to 40 ± 5 bursts min−1 following application of the vehicle on the ventral brainstem surface. CO2 had a similar effect in the presence of NE-52-QQ57 (1 mM) on the ventral brainstem surface (18 ± 4 to 41 ± 5 bursts min−1; p = 0.86, Fig. 6C). NE 52-QQ57 had no effect on other components of the hypercapnic respiratory response including increases in phrenic nerve burst amplitude (0.04 ± 0.01 to 0.06 ± 0.02V vs. 0.04 ± 0.02 to 0.06 ± 0.02V; p = 0.92) and minute ventilation (11 ± 4 to 34±8A.U vs. 11 ± 2 to 33±7A.U; p = 0.97). Direct application of NE 52-QQ57 to the ventral medulla had no effect on baseline respiratory activity (Fig. 6D). Reference: Neuropharmacology. 2018 Aug;138:381-392. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/29894771/

	Solvent	mg/mL	mM
Solubility
	DMSO	10.0	24.10
	Ethanol	45.0	108.00

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 416.53 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

In vitro protocol:

In vivo protocol:

1. Hosford PS, Mosienko V, Kishi K, Jurisic G, Seuwen K, Kinzel B, Ludwig MG, Wells JA, Christie IN, Koolen L, Abdala AP, Liu BH, Gourine AV, Teschemacher AG, Kasparov S. CNS distribution, signalling properties and central effects of G-protein coupled receptor 4. Neuropharmacology. 2018 Aug;138:381-392. doi: 10.1016/j.neuropharm.2018.06.007. Epub 2018 Jun 9. PMID: 29894771; PMCID: PMC6063991. 2. Velcicky J, Miltz W, Oberhauser B, Orain D, Vaupel A, Weigand K, Dawson King J, Littlewood-Evans A, Nash M, Feifel R, Loetscher P. Development of Selective, Orally Active GPR4 Antagonists with Modulatory Effects on Nociception, Inflammation, and Angiogenesis. J Med Chem. 2017 May 11;60(9):3672-3683. doi: 10.1021/acs.jmedchem.6b01703. Epub 2017 Apr 26. PMID: 28445047.

1: Liu H, Liu Y, Chen B. Antagonism of GPR4 with NE 52-QQ57 and the Suppression of AGE-Induced Degradation of Type II Collagen in Human Chondrocytes. Chem Res Toxicol. 2020 May 18. doi: 10.1021/acs.chemrestox.0c00111. Epub ahead of print. PMID: 32370492. 2: Hosford PS, Mosienko V, Kishi K, Jurisic G, Seuwen K, Kinzel B, Ludwig MG, Wells JA, Christie IN, Koolen L, Abdala AP, Liu BH, Gourine AV, Teschemacher AG, Kasparov S. CNS distribution, signalling properties and central effects of G-protein coupled receptor 4. Neuropharmacology. 2018 Aug;138:381-392. doi: 10.1016/j.neuropharm.2018.06.007. Epub 2018 Jun 9. PMID: 29894771; PMCID: PMC6063991.